MicroRNA (miRNA), small non-coding RNA, have been involved in regulation of the transcription and the translation of thousands of genes. Recently, it has been shown that Single-Nucleotide Polymorphisms (SNP) frequently alter microRNA-directed repression in mammals including humans but only in 3′-untranslated region25,26.
For instance, inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn disease and ulcerative colitis. Immunity Related GTPase, M (IRGM), involved in xerophagy and playing a role in the control of intracellular pathogens (like Mycobacterium tuberculosis) was found in genome wild association (GWA) studies as a risk associated locus for IBD, in particular the exonic synonymous mutation C313T (rs10065172; IRGM polymorphism in 313 position induce a nucleic change on the first base of the codon (CTG>TTG) and both codes for leucine amino acid) that is in strong linkage disequilibrium with a large deletion polymorphism upstream of the IRGM locus close to the promotor1,4.
This observation has led to the proposal that the deletion may be the cause of the difference of expression between the protective and the risk allele. However, until now despite strong computational analysis, no conserved transcription factor binding sequences on IRGM locus has been found within the deleted region that could explain the differences of expression between the risk and the protective allele.
It results thus that such synonymous mutation leading to a silent polymorphism with in the coding region of a gene of interest has never been shown as involved in the physiopathology of mammal diseases including human diseases by impairing the binding of related-miRNA with said gene of interest.